Abstract

Background

Central nervous system axons lack a robust regenerative response following spinal
cord injury (SCI) and regeneration is usually abortive. Supraspinal pathways, which
are the most commonly studied for their regenerative potential, demonstrate a limited
regenerative ability. On the other hand, propriospinal (PS) neurons, with axons intrinsic
to the spinal cord, have shown a greater regenerative response than their supraspinal
counterparts, but remain relatively understudied in regards to spinal cord injury.

Results

Utilizing laser microdissection, gene-microarray, qRT-PCR, and immunohistochemistry,
we focused on the intrinsic post-axotomy response of specifically labelled thoracic
propriospinal neurons at periods from 3-days to 1-month following T9 spinal cord injury.
We found a strong and early (3-days post injury, p.i) upregulation in the expression
of genes involved in the immune/inflammatory response that returned towards normal
by 1-week p.i. In addition, several regeneration associated and cell survival/neuroprotective
genes were significantly up-regulated at the earliest p.i. period studied. Significant
upregulation of several growth factor receptor genes (GFRa1, Ret, Lifr) also occurred
only during the initial period examined. The expression of a number of pro-apoptotic
genes up-regulated at 3-days p.i. suggest that changes in gene expression after this
period may have resulted from analyzing surviving TPS neurons after the cell death
of the remainder of the axotomized TPS neuronal population.

Conclusions

Taken collectively these data demonstrate that thoracic propriospinal (TPS) neurons
mount a very dynamic response following low thoracic axotomy that includes a strong
regenerative response, but also results in the cell death of many axotomized TPS neurons
in the first week after spinal cord injury. These data also suggest that the immune/inflammatory
response may have an important role in mediating the early strong regenerative response,
as well as the apoptotic response, since expression of all of three classes of gene
are up-regulated only during the initial period examined, 3-days post-SCI. The up-regulation
in the expression of genes for several growth factor receptors during the first week
post-SCI also suggest that administration of these factors may protect TPS neurons
from cell death and maintain a regenerative response, but only if given during the
early period after injury.